Dehydrogenases substrate specificity

N. Mukerjee, R. Peitruszko, Human Mitochondrial Aldehyde Dehydrogenase Substrate Specificity-Comparison of Esterase with Dehydrogenase Reaction , Arch. Biochem. Biophys. 1992, 299, 23-29. 

K. Vogel, K. L. Platt, P. Petrovic, A. Seidel, F. Oesch, Dihydrodiol Dehydrogenase Substrate Specificity, Inducibility and Tissue Distribution , Arch. Toxicol. 1982, Suppl. 5, 360 - 364. 

K. Palczewski, S. JSger, J. Buczylko, R. Crouch, D. L. Bredberg, K. P. Hofmann, M. A. Asson-Batres, and J. C. Saari. Rod outer segment retinol dehydrogenase substrate specificity and role in phototransduction. Biochemistry, 33, 13741-13750, 1994. 

Palczewski K, Jager S, Buczylko J, Crouch RK, Bredberg DL, Hofmaim KP, Asson-Batres MA, Saari JC (1994) Rod outer segment retinol dehydrogenase Substrate specificity and role in phototransduction. Biochemistry 33 13 741-13 750... 

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method for the production of chiral alcohols. HLAD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates (Table 11). It efficiendy reduces all simple four- to nine-membered cycHc ketones and also symmetrical and racemic cis- and trans-decalindiones (167). Asymmetric reduction of aUphatic acycHc ketones (C-4—C-10) (103,104) can be efficiendy achieved by alcohol dehydrogenase isolated from Thermoanaerohium hrockii (TBADH) (168). The enzyme is remarkably stable at temperatures up to 85°C and exhibits high tolerance toward organic solvents. Alcohol dehydrogenases from horse Hver and T. hrockii... 

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

Transfer of hydrogen from one substrate to another in a coupled oxidation-reduction reaction (Figure 11-3). These dehydrogenases are specific for their substrates but often utilize common coenzymes or hydrogen carriers, eg, NAD". Since the reactions are re-... 

Minteer and co-workers have also exploited the broad substrate specificity of PQQ-dependent alcohol dehydrogenase and aldehyde dehydrogenase from Gluconobacter species trapped within Nahon to oxidize either ethanol or glycerol at a fuel cell anode [Arechederra et al., 2007]. Although the alcohol dehydrogenase incorporates a series of heme electron transfer centers, it is unlikely that many enzyme molecules trapped within the mediator-free Nahon polymer are electronically engaged at the electrode. 

Zhu, D., Malik, H.T. and Hua, L. (2006) Asymmetric ketone reduction by a hyperthermophilic alcohol dehydrogenase. The substrate specificity enantioselectivity and tolerance of organic solvents. Tetrahedron Asymmetry, 17 (21), 3010-3014. 

The reactivity of xylitol in the polyol dehydrogenase reactions has been extensively studied for its relations to pentosuria. Xylitol was found to be oxidized in two ways (a) to L-xylulose by a highly specific NADP-requiring dehydrogenase and (b) to D-xylulose by a NAD-linked enzyme with lesser substrate specificity ... 

Most of the vanillic acid was reduced by E. coli containing Car in 2 h to vanillin (80 %) and vanillyl alcohol (20 %). Car does not reduce aldehydes to alcohols. However, E. coli s endogenous aldehyde reductase/dehydrogenase reduces vanillin to vanillyl alcohol. The broad substrate specificity of Car enables the wide application of this biocatalyst to other important applications, such as enantiomeric resolution of isomers such as ibuprofen and the reductions of many other natural and synthetic carboxylic acids. 

We have used a series of biocatalysts produced by site-directed mutations at the active site of L-phenylalanine dehydrogenase (PheDH) of Bacillus sphaericus, which expand the substrate specificity range beyond that of the wild-type enzyme, to catalyse oxidoreduc-tions involving various non-natural L-amino acids. These may be produced by enantiose-lective enzyme-catalysed reductive amination of the corresponding 2-oxoacid. Since the reaction is reversible, these biocatalysts may also be used to effect a kinetic resolution of a D,L racemic mixture. ... 

More than 2000 different enzymes are currently known. A system of classification has been developed that takes into account both their reaction specificity and their substrate specificity. Each enzyme is entered in the Enzyme Catalogue with a four-digit Enzyme Commission number (EC number). The first digit indicates membership of one of the six major classes. The next two indicate subclasses and subsubclasses. The last digit indicates where the enzyme belongs in the subsubclass. For example, lactate dehydrogenase (see pp. 98-101) has the EC number 1.1.1.27 (class 1, oxidoreductases subclass 1.1, CH-OH group as electron donor sub-subclass 1.1.1, NAD(P) " as electron acceptor). 

Bradshaw, C.W., Fu, H., Shen, G.J. and Wong, C.H. (1992) APseudomonas sp alcohol-dehydrogenase with broad substrate-specificity and unusual stereospecificity for organic-synthesis. J. Org. Chem., 57, 1526-1532. 

Roe DS, Vianey-Saban C, SharmaS, ZabotMT, Roe CR (2001) Oxidation of unsaturated fatty acids by human fibroblasts with very-long-chain acyl-CoA dehydrogenase deficiency aspects of substrate specificity and correlation with clinical phenotype. Clin Chim Acta 312 55-67... 

Singh, S.K. Matsuno, K. LaPorte, D.C. Banaszak, L.J. Crystal structure of Bacillus subtilis isocitrate dehydrogenase at 1.55 A. Insights into the nature of substrate specificity exhibited by Escherichia coli isocitrate dehydrogenase kinase/phosphatase. J. Biol. Chem., 276, 26154-26163 (2001)... 

Figure 16-6 shows schematically how the pyruvate dehydrogenase complex carries out the five consecutive reactions in the decarboxylation and dehydrogenation of pyruvate. Step CD is essentially identical to the reaction catalyzed by pyruvate decarboxylase (see Fig. 14-13c) C-l of pyruvate is released as C02, and C-2, which in pyruvate has the oxidation state of an aldehyde, is attached to TPP as a hydroxyethyl group. This first step is the slowest and therefore limits the rate of the overall reaction. It is also the point at which the PDH complex exercises its substrate specificity. In step (2) the hydroxyethyl group is oxidized to the level of a car-...

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method lor the production nf chiral alcohols. HI.AD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates. 

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